Process for the preparation of α-tocopherol

ABSTRACT

A process is provided for the preparation of α-tocopherol. According to the process, a condensation reaction between trimethylhydroquinone and a specific phytol derivative or isophytol is conducted in the presence of any one of the following solvents: 
     (i) a carbonate ester; 
     (ii) a lower fatty acid ester represented by the following formula: 
     
         R.sup.1 COOR.sup.2 
    
      wherein R 1  means a lower alkyl group having 1-4 carbon atoms and R 2  means a lower alkyl group having 1-5 carbon atoms with the proviso that methyl acetate and ethyl acetate are excluded; 
     (iii) a mixed solvent of a nonpolar solvent and a lower alcohol having 1-5 carbon atoms; and 
     (iv) a mixed solvent of the nonpolar solvent and the lower fatty acid ester.

This is a continuation-in-part of Ser. No. 08/826,504, now U.S. Pat. No.5,886,197 filed Apr. 3, 1997, which is a divisional of Ser. No.08/460,667, filed Jun. 2, 1995, now U.S. Pat. No. 5,663,376.

BACKGROUND OF THE INVENTION

a) Field of the Invention

This invention relates to a novel process for the preparation ofα-tocopherol useful as an antisterile vitamin, hypolipidemic, blood flowincreasing agent, oxygen radial scavenger, anticytosenility agent,antioxidant and the like.

b) Description of the Related Art

α-tocopherol has heretofore been prepared by condensingtrimethylhydroquinone represented by the following formula (I): ##STR1##with any one of phytols represented by the following formulae: ##STR2##in accordance with the Friedel-Crafts reaction ##STR3##

In this reaction, it is preferred to use a solvent, for example, tocontrol the reaction heat and/or to lower the viscosity of the reactionmixture. Specifically, ethyl acetate, hexane, benzene, toluene,methylene chloride or the like is used. Among these, ethyl acetate iscommonly used.

This common use of ethyl acetate as solvent for preparing α-tocopherolcan be attributed to its appropriate solubility fortrimethylhydroquinone (I) and also to its abundant availability at lowcost in industry.

Ethyl acetate, however, is accompanied by problems such that uponwashing a reaction mixture subsequent to the reaction, ethyl acetate iscaused to transfer at a high rate into a water layer, its recovery rateis low, and treatment of waste water from the washing is difficult.

Further, ethyl acetate is extremely prone to hydrolysis under conditionsother than neutral conditions, especially under basic conditions. Italso tends to undergo a transesterification. Due to these properties,there is a further problem that when ethyl acetate is employed in thepreparation of α-tocopherol, byproduction of α-tocopheryl acetate isunavoidable.

As α-tocopherol and α-tocopherol acetate have extremely closephysicochemical properties, they cannot be separated and purified by anyindustrial purification method such as molecular distillation.Nevertheless, α-tocopherol is required to have an extremely high puritywhen employed as medicines, a base material for cosmetics, foods or thelike. The preparation process of α-tocopherol, which makes use of ethylacetate as a solvent, has therefore been difficult to meet the demandfor such high-purity α-tocopherol.

On the other hand, use of a single kind of nonpolar solvent such ashexane, benzene or toluene tends to produce static electricity upon itscharging or its transfer through piping in a dry season such as winter,whereby inflammation and/or explosion hazards are involved.

As has been described above, the conventional preparation process ofα-tocopherol, which uses ethyl acetate or a single kind of nonpolarsolvent, is accompanied by many problems from the viewpoints of productpurity, economy, waste treatment, safety and the like, resulting in thelong-standing desire for an excellent industrial solvent which cansubstitute for such conventional solvents.

SUMMARY OF THE INVENTION

With a view toward improving the above-described problems of theconventional solvents, the present inventors have proceeded with anextensive investigation. As a result, it has been found that use of acarbonate ester (IV), a lower fatty acid ester (V) or a mixed solvent ofa nonpolar solvent (VI) and a lower alcohol having 1-5 carbon atoms(VII) or the lower fatty acid ester (V) as a solvent makes it possibleto industrially prepare α-tocopherol while attaining the above goal.This finding has led to the completion of the present invention.

An object of the present invention is therefore to provide anindustrially excellent process for the preparation of α-tocopherol whichis useful as an antisterile vitamin, hypolipidemic, blood flowincreasing agent, oxygen radial scavenger, anticytosenility agent,antioxidant and the like.

Here, trimethylhydroquinone (I) useful in the practice of the presentinvention is 2,3,5-trimethyl-1,4-hydroquinone and is represented by thefollowing formula: ##STR4##

On the other hand, the phytol derivative (II) is represented by thefollowing formula: ##STR5## wherein L means a hydroxy group, a halogenatom or an acetoxy, methanesulfonyloxy, ethanesulfonyloxy,benzenesulfonyloxy or toluenesulfonyloxy group.

Specific examples of the phytol derivative (II) include, but are notlimited to, the following compounds:

(1) phytol,

(2) phytyl chloride,

(3) phytyl bromide,

(4) phytyl iodide,

(5) phytyl acetate,

(6) phytyl methanesulfonate,

(7) phytyl ethanesulfonate,

(8) phytyl benzenesulfonate, and

(9) phytyl toluenesulfonate.

Next, the isophytol (III) is represented by the following formula:##STR6##

Further, specific examples of the carbonate ester (IV) include, but arenot limited to, the following compounds

(1) dimethyl carbonate,

(2) diethyl carbonate,

(3) dipropyl carbonate,

(4) methylethyl carbonate,

(5) ethylene carbonate, and

(6) propylene carbonate.

Among these, dimethyl carbonate, diethyl carbonate, methylethylcarbonate and propylene carbonate are more preferred.

In addition, the lower fatty acid ester (V) useful in the practice ofthe present invention is represented by the following formula:

    R.sup.1 COOR.sup.2                                         (V)

wherein R¹ means a lower alkyl group having 1-4 carbon atoms and R²means a lower alkyl group having 1-5 carbon atoms with the proviso thatmethyl acetate and ethyl acetate are excluded. This means that neithermethyl acetate nor ethyl acetate is used as the lower fatty acid ester(V) in the present invention. Specific examples of the lower fatty acidester (V) include, but are not limited to, the following compounds:

(1) n-propyl acetate,

(2) i-propyl acetate,

(3) n-butyl acetate,

(4) i-butyl acetate,

(5) t-butyl acetate,

(6) n-amyl acetate,

(7) i-amyl acetate [CH₃ COOCH₂ CH₂ CH(CH₃)₂ ],

(8) sec-amyl acetate [CH₃ COOCH(CH₃)CH₂ CH₂ CH₃ ],

(9) t-amyl acetate [CH₃ COOC(CH₃)₂ CH₂ CH₃ ],

(10) 2,2-dimethylpropyl acetate [CH₃ COOCH₂ C(CH₃)₃ ],

(11) 2-methylbutyl acetate [CH₃ COOCH₂ CH(CH₃)CH₂ CH₃ ],

(12) methyl propionate,

(13) n-butyl propionate,

(14) ethyl butyrate,

(15) i-propyl butyrate,

(16) methyl isobutyrate,

(17) ethyl isobutyrate,

(18) i-butyl isobutyrate,

(19) methyl valerate,

(20) ethyl valerate,

(21) methyl isovalerate,

(22) ethyl isovalerate,

(23) methyl pivalate, and

(24) ethyl pivalate.

Of these, more preferred are n-propyl acetate, i-propyl acetate, n-butylacetate, i-butyl acetate, n-butyl propionate, ethyl butyrate, i-propylbutyrate, methyl isobutyrate, ethyl isobutyrate, methyl valerate, ethylisovalerate and ethyl pivalate.

On the other hand, specific examples of the nonpolar solvent (VI)include, but are not limited to, the following compounds:

(1) pentane,

(2) hexane,

(3) heptane,

(4) octane,

(5) ligroin,

(6) petroleum ether,

(7) cyclohexane,

(8) benzene,

(9) toluene, and

(10) xylene.

Of these, more preferred are hexane, heptane, ligroin, cyclohexane,toluene and xylene.

Finally, specific examples of the lower alcohol having 1-5 carbon atoms(VII) include, but are not limited to, the following compounds:

(1) methanol,

(2) ethanol,

(3) n-propanol,

(4) i-propanol,

(5) n-butanol,

(6) i-butanol,

(7) t-butanol,

(8) n-amyl alcohol (also called "1-pentanol"),

(9) 2-pentanol (also called "1-methyl-1-butanol"),

(10) 3-pentanol (also called "1-ethyl-1-propanol"),

(11) i-amyl alcohol (also called "3-methyl-1-butanol"),

(12) t-amyl alcohol (also called "1,1-dimethyl-1-propanol"),

(13) 2,2-dimethyl-1-propanol,

(14) 1,2-dimethyl-1-propanol,

(15) 2-methyl-1-butanol, and

(16) 3-methyl-2-butanol.

Of these, more preferred are n-propanol, i-propanol, n-butanol,i-butanol, t-butanol, n-amyl alcohol, 2-pentanol, 3-pentanol, i-amylalcohol and t-amyl alcohol.

The preparation process according to the present invention willhereinafter be described in detail.

The process according to the present invention for the preparation ofα-tocopherol features that in a condensation reaction betweentrimethylhydroquinone (I) and the phytol derivative (II) or isophytol(III), the reaction is conducted in the presence of the carbonate ester(IV), the lower fatty acid ester (V), or the mixed solvent of thenonpolar solvent (VI) and the lower alcohol having 1-5 carbon atoms(VII) or the lower fatty acid ester (V). Accordingly, one of thefollowing solvents is employed:

(1) carbonate ester (IV),

(2) lower fatty acid ester (V),

(3) mixed solvent of the nonpolar solvent (VI) and the lower alcoholhaving 1-5 carbon atoms (VII), and

(4) mixed solvent of the nonpolar solvent (VI) and the lower fatty acidester (V).

When the mixed solvent of the nonpolar solvent (VI) and the loweralcohol having 1-5 carbon atoms (VII) or the lower fatty acid ester (V)is used, no particular limitation is imposed on their mixing ratio. Ingeneral, however, the lower alcohol having 1-5 carbon atoms (VII) or thelower fatty acid ester (V) is added in a proportion of 0.1-50 vol. %,preferably 0.5-25 vol. %, more preferably 1-15 vol. % to the nonpolarsolvent (VI), followed by mixing for use in the reaction.

Although no particular limitation is imposed on the amount of thesolvent to be employed, the solvent is used generally in an amount ofabout 0.5-100 ml per gram of trimethylhydroquinone (I), with about0.7-50 ml being preferred and about 1-20 ml more preferred. It is to benoted that the solvent can be used either singly or as a mixture with anadditional solvent.

When an additional solvent is used, no particular limitation is imposedthereon insofar as it is inert to trimethylhydroquinone (I), the phytolderivative (II), isophytol (III) or a catalyst. Specific examples ofsuch an additional solvent include the following solvents:

Benzene, toluene, xylene, nitrobenzene, chlorobenzene, dichlorobenzene,nitromethane, tetrahydrofuran, 1,2-dimethoxyethane, ethyl ether,isopropyl ether, butyl ether, methyl acetate, ethyl acetate, propylacetate, methyl propionate, ethyl propionate, methyl butyrate, ethylbutyrate, acetone, 2-butanone (methyl ethyl ketone), 3-pentanone(diethyl ketone), 3-hexanone (ethyl propyl ketone), 4-heptanone(dipropyl ketone), 2,4-dimethyl-3-pentanone (diisopropyl ketone), propylalcohol, butyl alcohol, pentanol, t-amyl alcohol, hexane, octane,decane, decalin, cyclohexane, methylene chloride, chloroform, carbontetrachloride, 1,2-dichloroethane, 1,1,1-trichloroethane,1,1,2-trichloroethane, trichlene, 1,1,1,2-tetrachloroethane,1,1,2,2-tetrachloroethane, 1-chloropropane, 2-chloropropane,1,1-dichloropropane, 1,2-dichloropropane, 1,3-dichloropropane,2,2-dichloropropane, 1,4-,dioxane, and 1,3-dioxolane.

The preparation process of the present invention can be conducted in amanner known per se in the art with respect to the Friedel-Craftsreaction. In general, trimethylhydroquinone (I), a catalyst and asolvent are mixed, to which the phytol derivative (II) or isophytol(III) is added in an amount of about 0.9-1.1 equivalents based on thetrimethylhydroquinone (I). Although it is preferred to conduct thereaction under a stream of an inert gas such as nitrogen or argon, thereaction can also be conducted without such an inert gas. No limitationis therefore imposed on the environment for the reaction.

The term "catalyst" as used herein means a catalyst commonly employed inthe Friedel-Crafts reaction, such as a mineral acid, Lewis acid, acidicion-exchange resin, or a triflate, nitrate or sulfate of scandium,yttrium or a lanthanoid element. Although no particular limitation isimposed on the amount of the catalyst to be used, the catalyst is usedgenerally in a proportion of about 0.001-1.5 equivalents based ontriethylhydroquinone (I), with about 0.005-1.0 equivalent beingpreferred and about 0.01-0.5 equivalent more preferred. Such catalystcan be used either singly or in combination. In addition, a co-catalystsuch as hydrochloric acid, sulfuric acid, phosphoric acid orp-toluenesulfonic acid can also be added.

The reaction in the present invention can be conducted at a temperaturein a range of from ice cooled temperature to the reflux temperature ofthe solvent. At room temperature, the reaction is generally brought tocompletion in 1-12 hours or so. The reaction time can be shortened byconducting reaction under heat of about 100° C. or under reflux.Depending on the catalyst, it is also possible to shorten the reactiontime further by azeotropically eliminating water.

α-tocopherol so prepared can be purified by a method known per se in theart, such as silica gel column chromatography, HPLC or moleculardistillation.

To specifically describe the present invention, comparative examples andexamples will be described next. Needless to say, the present inventionis by no means limited to or by them.

COMPARATIVE EXAMPLE 1 Synthesis of α-tocopherol (solvent: ethyl acetate)##STR7##

To a mixture consisting of 23.3 g (0.153 mol) of2,3,5-trimethylhydroquinone, 17.5 g (0.128 mol) of zinc chloride, 54 mlof ethyl acetate and 2.5 g of concentrated hydrochloric acid, 46.1 g(0.153 mol) of isophytol (purity: 98.3%) was added dropwise understirring at 25-30° over 3 hours. At the same temperature, the reactionmixture was stirred for an additional 2 hours. After the reactionmixture was washed with 10 ml of water, the solvent was distilled off.Toluene (100 ml) was added to the residue to dissolve the same. Theresulting solution was washed successively with water, alkaline waterand a saturated aqueous solution of NaCl, dried over magnesium sulfateand then concentrated under reduced pressure, whereby 66.0 g of thetitle compound was obtained as a brown oil (yield: 95.2%, GLC purity:95.1%, α-tocopheryl acetate content: 2.0%, ethyl acetate recovery rate:50%).

COMPARATIVE EXAMPLES 2-8 Synthesis of α-tocopherol (conventionalsolvents)

The procedures of Comparative Example 1 were repeated by changing thesolvent. The following results were obtained.

                  TABLE 1                                                         ______________________________________                                        Results of Synthesis of α-tocopherol                                      by Conventional Solvents                                                      Comparative             Yield Yield GLC purity                                Example Solvent (g) (%) (%)                                                 ______________________________________                                        2       toluene       64.2    91.6  94.0                                        3 heptane 64.5 93.3 95.3                                                      4 cyclohexane 63.0 90.5 94.7                                                  5 diethyl ketone 60.4 86.5 94.4                                               6 methyl isobutyl ketone 67.4 97.7 95.6                                       7 ligroin 66.3 83.1 82.6                                                      8 n-butanol 66.2 56.2 55.9                                                  ______________________________________                                    

EXAMPLE 1 Synthesis of α-tocopherol (solvent: isobutyl acetate) ##STR8##

To a mixture consisting of 23.3 g (0.153 mol) of2,3,5-trimethylhydroquinone, 17.5 g (0.128 mol) of zinc chloride, 50 mlof isobutyl acetate and 2.5 g of concentrated hydrochloric acid, 46.1 g(0.153 mol) of isophytol (purity: 98.3%) were added dropwise understirring at 30-40° C. over 3 hours. At the same temperature, thereaction mixture was stirred for an additional 2 hours. After thereaction mixture was washed with 10 ml of water, the solvent wasdistilled off. Toluene (100 ml) was added to the residue to dissolve thesame. The resulting solution was washed successively with water,alkaline water and a saturated aqueous solution of NaCl, dried overmagnesium sulfate and then concentrated under reduced pressure, whereby67.0 g of the title compound was obtained as a brown oil (yield: 98.6%,GLC purity: 98.6%, α-tocopheryl acetate content: 0.2%, isobutyl acetaterecovery rate: 92%).

EXAMPLE 2 Synthesis of α-tocopherol (solvent: isobutyl acetate)

To a mixture consisting of 69.9 g (0.460 mol) of2,3,5-trimethylhydroquinone, 52.5 g (0.386 mol) of zinc chloride, 150 mlof isobutyl acetate and 7.5 g of concentrated hydrochloric acid, 138.3 g(0.459 mol) of isophytol (purity: 98.3%) was added dropwise understirring at 30-40° C. over 3 hours. At the same temperature, thereaction mixture was stirred for an additional 2 hours. After thereaction mixture was washed with 30 ml of water, the solvent wasdistilled off. Toluene (300 ml) was added to the residue to dissolve thesame. The resulting solution was washed successively with water,alkaline water and a saturated aqueous solution of NaCl, dried overmagnesium sulfate and then concentrated under reduced pressure, whereby202.0 g of the title compound was obtained as a brown oil (yield 99.6%,GLC purity: 97.5).

EXAMPLES 3-5 Synthesis of α-tocopherol (solvents: acetate esters)

The procedures of Example 1 were repeated by changing the solvent. Thefollowing results were obtained.

                  TABLE 2                                                         ______________________________________                                        Results of Synthesis of α-tocopherol                                      by Acetate Ester Solvents                                                                             Yield Yield GLC purity                                Example Solvent (g) (%) (%)                                                 ______________________________________                                        3       n-propyl acetate                                                                            67.0    98.3  96.7                                        4 i-propyl acetate 66.8 97.9 96.6                                             5 n-butyl acetate 66.9 98.5 97.0                                            ______________________________________                                    

EXAMPLES 6-13 Synthesis of α-tocopherol (solvents: other lower fattyacid esters)

The procedures of Example 1 were repeated by changing the solvent. Thefollowing results were obtained.

                  TABLE 3                                                         ______________________________________                                        Results of Synthesis of α-tocopherol                                      by Lower Fatty Acid Esters                                                                            Yield Yield GLC purity                                Example Solvent (g) (%) (%)                                                 ______________________________________                                        6       n-butyl propionate                                                                          67.0    98.6  97.0                                        7 ethyl butyrate 66.8 98.5 97.2                                               8 i-propyl butyrate 66.5 98.0 97.1                                            9 methyl isobutyrate 66.6 98.4 97.4                                           10 ethyl isobutyrate 66.5 98.0 97.1                                           11 methyl valerate 66.3 97.4 96.8                                             12 ethyl isovalerate 66.2 97.3 96.9                                           13 ethyl pivalate 66.0 96.8 96.7                                            ______________________________________                                    

EXAMPLE 14 Synthesis of α-tocopherol (solvent: diethyl carbonate)

To a mixture consisting of 23.3 g (0.153 mol) of2,3,5-trimethylhydroquinone, 17.5 g (128 mol) of zinc chloride, 50 ml ofdiethyl carbonate and 2.5 g of concentrated hydrochloric acid, 46.1 g(0.153 mol) of isophytol (purity: 98.3%) was added dropwise understirring at 30-40° C. over 3 hours. At the same temperature, thereaction mixture was stirred for an additional 2 hours. After thereaction mixture was washed with 10 ml of water, the solvent wasdistilled off. Toluene (100 ml) was added to the residue to dissolve thesame. The resulting solution was washed successively with water,alkaline water and a saturated aqueous solution of NaCl, dried overmagnesium sulfate and then concentrated under reduced pressure, whereby67.0 g of the title compound was obtained as a brown oil (yield: 98.9%,GLC purity: 97.3%).

EXAMPLE 15 Synthesis of α-tocopherol (solvent: diethyl carbonate)

To a mixture consisting of 69.9 g (0.460 mol) of2,3,5-trimethylhydroquinone, 52.5 g (0.386 mol) of zinc chloride, 150 mlof diethyl carbonate and 7.5 g of concentrated hydrochloric acid, 138.3g (0.459 mol) of isophytol (purity: 98.3%) was added dropwise understirring at 30-40° C. over 3 hours. At the same temperature, thereaction mixture was stirred for an additional 2 hours. After thereaction mixture was washed with 30 ml of water, the solvent wasdistilled off. Toluene (300 ml) was added to the residue to dissolve thesame. The resulting solution was washed successively with water,alkaline water and a saturate aqueous solution of NaCl, dried overmagnesium sulfate and then concentrated under reduced pressure, whereby201.2 g of the title compound was obtained as a brown oil (yield:99.2%), GLC purity: 97.5%).

EXAMPLES 16-19 Synthesis of α-tocopherol (solvents: carbonate esters)

The procedures of Example 14 were repeated by changing the solvent. Thefollowing results were obtained.

                  TABLE 4                                                         ______________________________________                                        Results of Synthesis of α-tocopherol                                      by Carbonate Ester Solvents                                                                           Yield Yield GLC purity                                Example Solvent (g) (%) (%)                                                 ______________________________________                                        16     dimethyl carbonate                                                                           66.5    97.7  96.8                                        17 ethylene carbonate 67.0 94.0 92.5                                          18 propylene carbonate 66.6 97.2 96.2                                         19 methylethyl carbonate 66.0 97.2 97.0                                     ______________________________________                                    

EXAMPLE 20 Synthesis of α-tocopherol (solvent: hexane/n-butanol mixedsolvent system)

To a mixture consisting of 23.3 g (0.153 mol) of2,3,5-trimethylhydroquinone, 17.5 g (0.128 mol) of zinc chloride, 47.5ml of hexane, 2.5 ml of n-butanol and 2.5 g of concentrated hydrochloricacid, 46.1 g (0.153 mol) of isophytol (purity: 98.3%) was added dropwiseunder stirring at 30-40° C. over 3 hours. At the same temperature, thereaction mixture was stirred for an additional 2 hours. After thereaction mixture was washed with 10 ml of water, the solvents weredistilled off. Toluene (100 ml) was added to the residue to dissolve thesame. The resulting solution was washed successively with water,alkaline water and a saturated aqueous solution of NaCl, dried overmagnesium sulfate and then concentrated under reduced pressure, whereby65.0 g of the title compound was obtained as a brown oil (yield: 95.9%,GLC purity: 97.2%).

EXAMPLE 21 Synthesis of α-tocopherol (solvent: hexane/n-butanol mixessolvent system)

To a mixture consisting of 69.9 g (0.460 mol) of2,3,5-trimethylhydroquinone, 52.5 g (0.386 mol) of zinc chloride, 142.5ml of hexane, 7.5 ml of n-butanol and 7.5 g of concentrated hydrochloricacid, 138.3 g (0.459 mol) of isophytol (purity: 98.3%) was addeddropwise under stirring at 30-40° C. over 3 hours. At the sametemperature, the reaction mixture was stirred for an additional 2 hours.After the reaction mixture was washed with 30 ml of water, the solventswere distilled off. Toluene (300 ml) was added to the residue todissolve the same. The resulting solution was washed successively withwater, alkaline water and a saturated aqueous solution of NaCl, driedover magnesium sulfate and then concentrated under reduced pressure,whereby 200 g of the title compound was obtained as a brown oil yield98.1%, GLC purity: 97.0%).

EXAMPLES 22-29 Synthesis of α-tocopherol (solvents: mixed solventsystems)

The procedures of Examples 21 were repeated by changing the solvents.The following results were obtained.

                  TABLE 5                                                         ______________________________________                                        Results of Synthesis of α-tocopherol                                      by Mixed Solvent Systems                                                                              Yield Yield GLC purity                                Example Solvent (g) (%) (%)                                                 ______________________________________                                        22     hexane + 5% isobutyl                                                                         65.4    96.0  96.7                                         acetate                                                                      23 toluene + 5% n-propanol 66.2 95.5 95.1                                     24 heptane + 5% n-butanol 64.0 94.1 96.9                                      25 cyclohexane + 5% 65.5 95.8 96.4                                             n-butanol                                                                    26 toluene + 5% n-butanol 64.5 92.8 94.8                                      27 ligroin + 5% n-butanol 66.5 95.8 94.9                                      28 toluene + 5% n-pentanol 67.3 94.5 92.5                                     29 toluene + 5% 69.4 96.6 91.7                                                 t-amyl alcohol                                                             ______________________________________                                    

EXAMPLE 30 Synthesis of dl-α-tocopherol

To a mixture consisting of 23.3 g (0.153 mol) of2,3,5-trimethylhydroquinone, 23.2 g (0.153 mol) of zinc bromide, 52.9 mlof diethyl carbonate and 4.3 g of 47% hydrobromic acid, was addeddropwise, under stirring at 50±5° C. over one hour, 46.2 g (0.153 ml) ofisophytol (purity: 98.1%). Further, the resulting mixture was stirredfor one hour at the same temperature. The reaction liquid was washedseveral times with 50 ml of water, followed by concentrating under areduced pressure, whereby 66.7 g of the title compound was obtained as abrown oil (yield: 99.1 %, GLC purity: 98.0%).

EXAMPLES 31 AND 32 Synthesis of dl-α-tocopherol

The procedures of Example 30 were repeated by changing the solvents. Thefollowing results were obtained.

                  TABLE 6                                                         ______________________________________                                        Results of Synthesis of α-tocopherol                                      by Mixed Solvent Systems                                                                              Yield Yield GLC purity                                Example Solvent (g) (%) (%)                                                 ______________________________________                                        31     dimethyl carbonate                                                                           66.5    98.1  97.3                                        32 methyl ethyl carbonate 66.7 98.6 97.5                                    ______________________________________                                    

EXAMPLE 33 Synthesis of dl-α-tocopherol

To a mixture consisting of 69.9 g (0.460 mol) of2,3,5-trimethylhydroquinone, 69.7 g (0.31 mol) of zinc bromide, 7.5 g ofconcentrated hydrochloric acid and 1.2 g of zinc dust, was addeddropwise, under stirring at 50° C. over 1 hour, 138.8 g (0.460 mol) ofisophytol (purity: 98.1%). Further, the resulting mixture was stirred atthe same temperature for 1 hour. The reaction liquid was washed withwater, followed by concentrating, whereby 199.4 g of the title compoundwas obtained as a brown oil (yield: 98.6%, GLC purity: 97.8%).

What is claimed is:
 1. A process for the preparation of α-tocopherol bya condensation reaction between trimethylhydroquinone represented by thefollowing formula (I): ##STR9## and a phytol derivative represented bythe following formula (II): ##STR10## wherein L means a hydroxy group, ahalogen atom, an acetoxy, methanesulfonyloxy, ethanesulfonyloxy,benzenesulfonyloxy or toluenesulfonyloxy group, or isophytol representedby the following formula (III): ##STR11## which comprises conducting thecondensation reaction in the presence of a carbonate ester as a solventand Lewis acid excepting for ZnCl₂ as a catalyst.
 2. The process for thepreparation of α-tocopherol as claimed in claim 1, wherein the Lewisacid is ZnBr₂.